growth plates fuse at the end of puberty.
Cell Growth: Treatment with pituitary-derived human growth hormone results in an increase in both the number and the size of skeletal muscle cells.
Organ Growth: Growth hormone of human pituitary origin influences the size and function of internal organs and increases red cell mass. Saizen® has been shown to promote similar organ weight increase to pituitary human growth hormone in an adequate animal model.
Protein Metabolism–Linear growth is facilitated in part by growth hormone-stimulated protein synthesis. This is reflected by increased cellular uptake of amino acids and nitrogen retention as demonstrated by a decline in urinary nitrogen excretion and blood urea nitrogen during growth hormone therapy.
Carbohydrate Metabolism–Growth hormone is a modulator of carbohydrate metabolism. Children with inadequate secretion of growth hormone sometimes experience fasting hypoglycemia that is improved by treatment with growth hormone. Saizen® therapy may decrease glucose tolerance. Administration of Saizen® to normal adults and patients with growth hormone deficiency resulted in transient increases in mean serum fasting and postprandial insulin levels. However, glucose levels remained in the normal range.
Lipid Metabolism–Acute administration of human growth hormone to humans results in lipid mobilization. Nonesterified fatty acids increase in plasma within one hour of Saizen® administration. In growth hormone deficient patients, long-term growth hormone administration often decreases body fat. Mean cholesterol levels decreased in patients treated with Saizen®. The clinical significance of this is unknown.
Mineral Metabolism– Growth hormone administration results in the retention of total body potassium, phosphorus, and sodium. Serum calcium levels appear to be unaffected.
Connective Tissue/Bone Metabolism–Growth hormone stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.
Pharmacokinetics
Absorption - The absolute bioavailability of recombinant human growth hormone (r-hGH) after subcutaneous administration ranges between 70-90%.
Distribution - The mean volume of distribution of r-hGH given to healthy volunteers was estimated to be 12.0 ± 1.08 L.
Metabolism - The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products is returned to the systemic circulation. The mean half-life of intravenous somatropin in normal males is 0.6 hours, whereas subcutaneously and intramuscularly administered somatropin has a half-life of 1.75 and 3.4 hours, respectively. The longer half-life observed after subcutaneous or intramuscular administration is due to slow absorption from the injection site.
Excretion - The mean clearance of intravenously administered r-hGH in six normal male volunteers was 14.6 ± 2.8 L/hr.
Special Populations
Pediatric - The pharmacokinetics of r-hGH is similar in children and adults.
Gender - No gender studies have been performed in children. In adults, the clearance of r-hGH in both men and women tends to be similar.
Race - No data are available.
Renal Insufficiency - Children and
